Porphyromonas gingivalis in Alzheimer’s disease: Association with salivary lactoferrin and inflammatory response

Recent evidence has highlighted the role of the oral microbiome in the inflammatory response and pathogenesis of Alzheimer's disease (AD). The oral pathogen Porphyromonas gingivalis (P. gingivalis) and its gingipain virulence factors may be involved in the development of AD. Concurrently, a decline in the antimicrobial protein lactoferrin has been observed in AD saliva. In this study, we analyzed whether the presence of P. gingivalis and gingipain were associated with salivary lactoferrin and inflammatory markers in patients with AD, mild cognitive impairment (MCI) and age-matched controls. Salivary presence of P. gingivalis was higher in MCI and AD patients and exhibited a negative correlation with global cognitive function. We further showed a marked reduction in salivary lactoferrin with AD progression. Salivary/plasma levels of pro-inflammatory and anti-inflammatory cytokines were significantly higher and lower, respectively, in MCI and AD patients compared to controls. Specifically, salivary levels of Interleukin-6 (IL-6) and IL-23 were higher in MCI and AD patients compared to controls, while the IL-1 receptor antagonist (IL-1ra) and IP-10 were reduced in both saliva and plasma in AD patients. Moreover, stromal cell derived factor 1α (SDF1α)/CXCL12, macrophage inflammatory protein-1β (MIP-1β), and vascular endothelial growth factor (VEGF) salivary and plasma levels were reduced in AD patients. Correlation analyses revealed an inverse relationship between salivary lactoferrin and bacterial load and cytokine concentrations. Our findings suggest that AD is associated with alterations to the oral environment, as revealed by higher P. gingivalis presence, lower lactoferrin levels and elevated pro-inflammatory cytokines.